公开(公告)号：US07759379B2

公开(公告)日：2010-07-20

申请号：US11627518

申请日：2007-01-26

Applicant: Hartmut Strobel ,  Sven Ruf ,  Dominique Lesuisse ,  Conception Nemecek ,  Youssef El-Ahmad ,  Stefan Guessregen ,  Anne Lebrun ,  Kurt Ritter ,  Didier Benard ,  Augustin Hittinger ,  Hervé Bouchard

Inventor： Hartmut Strobel ,  Sven Ruf ,  Dominique Lesuisse ,  Conception Nemecek ,  Youssef El-Ahmad ,  Stefan Guessregen ,  Anne Lebrun ,  Kurt Ritter ,  Didier Benard ,  Augustin Hittinger ,  Hervé Bouchard

IPC: C07D239/02 ,  A61K31/505 ,  A61P43/00

CPC classification number: C07D403/04

Abstract: The invention relates to compounds of formula (I): in which R1, R2, L1, X, R3, A, R4, R4′, R4″, R4″′, R5, Y and L2 are as herein defined, salts and prodrugs thereof, to their use as protein kinase inhibitors, and to methods of treating diseases comprising adminstration thereof.

Abstract translation: 本发明涉及式（I）化合物：其中R1，R2，L1，X，R3，A，R4，R4'，R4“，R4”'，R5，Y和L2如本文所定义， 作为蛋白激酶抑制剂的用途，以及治疗包括其施用的疾病的方法。

公开(公告)号：US07713963B2

公开(公告)日：2010-05-11

申请号：US11548501

申请日：2006-10-11

Applicant: Hartmut Strobel ,  Paulus Wohlfart ,  Alena Safarova ,  Armin Walser ,  Teri Suzuki ,  Karl Schoenafinger ,  Ramalinga M. Dharanipragada

Inventor： Hartmut Strobel ,  Paulus Wohlfart ,  Alena Safarova ,  Armin Walser ,  Teri Suzuki ,  Karl Schoenafinger ,  Ramalinga M. Dharanipragada

IPC: A61K31/541 ,  A61K31/5377 ,  C07D417/02 ,  C07D413/02

CPC classification number: C07D213/81 ,  C07C233/58 ,  C07C233/65 ,  C07C233/66 ,  C07C233/74 ,  C07C233/76 ,  C07C235/42 ,  C07C235/54 ,  C07C235/84 ,  C07C237/38 ,  C07C237/42 ,  C07C255/57 ,  C07C255/60 ,  C07C309/66 ,  C07C309/73 ,  C07C311/08 ,  C07C311/16 ,  C07C311/21 ,  C07C317/44 ,  C07C323/62 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2602/08 ,  C07D207/34 ,  C07D213/56 ,  C07D213/82 ,  C07D215/48 ,  C07D235/08 ,  C07D241/24 ,  C07D249/04 ,  C07D261/18 ,  C07D295/185 ,  C07D307/78 ,  C07D307/84 ,  C07D317/60 ,  C07D333/24 ,  C07D401/06

Abstract: The present invention relates to acylated indanyl amines according to the general formula (I) wherein R1—R4 have the meanings given in the description, A is CH2, CHOH or CH—(C1-C3-alkyl), B is CH2 or CH—(C1-C3-alkyl), and R5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description. These compounds are useful in the upregulation of endothelial nitric oxide synthase (eNOS), and may therefore be useful for the manufacture of medicaments for the treatment of cardiovascular diseases, stable or unstable angina pectoris, coronary heart disease, Prinzmetal angina, acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes or diabetes complications, nephropathy or retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, restricted memory performance, a restricted ability to learn, or for the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives.

Abstract translation: 本发明涉及根据通式（I）的酰化茚满基胺，其中R 1 -R 4具有在描述中给出的含义，A是CH 2，CHOH或CH-（C 1 -C 3 - 烷基），B是CH 2或CH- （C 1 -C 3 - 烷基），R 5是可以被描述中所列取代基取代的芳基或杂芳基。 这些化合物可用于内皮一氧化氮合酶（eNOS）的上调，因此可用于制备用于治疗心血管疾病，稳定或不稳定型心绞痛，冠心病，Prinzmetal心绞痛，急性冠状动脉综合征， 心脏衰竭，心肌梗塞，中风，血栓形成，外周动脉闭塞性疾病，内皮功能障碍，动脉粥样硬化，再狭窄，PTCA后的内皮损伤，高血压，原发性高血压，肺动脉高压，继发性高血压，肾血管性高血压，慢性肾小球肾炎，勃起功能障碍，室性心律失常， 糖尿病或糖尿病并发症，肾病或视网膜病变，血管生成，支气管哮喘，慢性肾功能衰竭，肝硬化，骨质疏松症，受限记忆能力，受限的学习能力或降低绝经后妇女的心血管危险或摄入避孕药 。

公开(公告)号：US20100004299A1

公开(公告)日：2010-01-07

申请号：US12466576

申请日：2009-05-15

Applicant: Gerhard ZOLLER ,  Hartmut STROBEL ,  David William WILL ,  Paulus WOHLFART

Inventor： Gerhard ZOLLER ,  Hartmut STROBEL ,  David William WILL ,  Paulus WOHLFART

IPC: A61K31/429 ,  C07D513/04 ,  A61P9/10

CPC classification number: C07D513/04

Abstract: The present invention relates to derivatives of imidazo[2,1-b]thiazoles of formula I, in which R, R1 to R3 and n have the meanings indicated in the claims, which modulate the transcription of endothelial nitric oxide (NO) synthase and are valuable pharmacologically active compounds. Specifically, the compounds of formula I upregulate the expression of the enzyme endothelial NO synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention further relates to processes for the preparation of compounds of formula I, to pharmaceutical compositions comprising them, and to the use of compounds of formula I for the manufacture of a medicament for the stimulation of the expression of endothelial NO synthase or for the treatment of various diseases including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency, for example.

Abstract translation: 本发明涉及式I的咪唑并[2,1-b]噻唑衍生物，其中R，R 1至R 3和n具有权利要求中所示的含义，其调节内皮一氧化氮（NO）合酶的转录和 是有价值的药理活性化合物。 具体地，式I化合物上调酶内皮NO合成酶的表达，并且可以在需要增加所述酶的表达或增加的NO水平或降低的NO水平的标准化的条件下使用。 本发明还涉及制备式I化合物的方法，包含它们的药物组合物，以及式I化合物在制备用于刺激内皮NO合成酶表达或用于治疗的药物中的用途 包括心血管疾病如动脉粥样硬化，血栓形成，冠状动脉疾病，高血压和心功能不全等各种疾病。

公开(公告)号：US20090082329A1

公开(公告)日：2009-03-26

申请号：US12173191

申请日：2008-07-15

Applicant: Frank HALLEY ,  Youssef EL-AHMAD ,  Victor CERTAL ,  Corinne VENOT ,  Anne DAGALLIER ,  Hartmut STROBEL ,  Kurt RITTER ,  Sven RUF

Inventor： Frank HALLEY ,  Youssef EL-AHMAD ,  Victor CERTAL ,  Corinne VENOT ,  Anne DAGALLIER ,  Hartmut STROBEL ,  Kurt RITTER ,  Sven RUF

IPC: A61K31/4545 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  A61K31/506 ,  A61K31/496 ,  A61P3/00 ,  A61P37/00 ,  A61P11/00 ,  A61P35/00 ,  A61P9/00 ,  C12N9/99 ,  A61K31/5377 ,  C07D403/14 ,  C07D413/06 ,  A61K31/4439

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14

Abstract: The disclosure relates to compounds of formula (I): wherein Ra, Rb, R, and n are as defined in the disclosure, to pharmaceutical compositions comprising said compounds, and to processes for making and methods of using the same.

Abstract translation: 本公开涉及式（I）化合物：其中Ra，Rb，R和n如本公开所定义，包含所述化合物的药物组合物，及其制备方法及其使用方法。

公开(公告)号：US07309579B2

公开(公告)日：2007-12-18

申请号：US11144265

申请日：2005-06-03

Applicant: Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

Inventor： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

IPC: C12Q1/48

CPC classification number: C12Q1/527 ,  G01N2333/795 ,  G01N2500/00

Abstract: The invention relates to methods for detecting a soluble guanylate cyclase whose heme iron is in the trivalent oxidation state, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase when the heme iron of at least part of this soluble guanylate cyclase is oxidized to the trivalent state and also to diagnostic aids or kits for detecting a soluble guanylate cyclase with trivalent heme iron. Further, the invention relates methods for detecting a soluble guanylate cyclase lacking a heme group, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase lacking a heme group.

Abstract translation: 本发明涉及用于检测其血红素铁处于三价氧化状态的可溶性鸟苷酸环化酶的方法，以及当该可溶性鸟苷酸环化酶的至少一部分的血红素铁时，发现刺激可溶性鸟苷酸环化酶活性的化学物质的方法 被氧化成三价状态，也用于用三价血红素铁检测可溶性鸟苷酸环化酶的诊断辅助剂或试剂盒。 此外，本发明涉及用于检测缺少血红素基团的可溶性鸟苷酸环化酶的方法，以及用于发现刺激缺少血红素基团的可溶性鸟苷酸环化酶的活性的化学物质的方法。

公开(公告)号：US20050227308A1

公开(公告)日：2005-10-13

申请号：US11144265

申请日：2005-06-03

Applicant: Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

Inventor： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

IPC: G01N33/50 ,  C12Q1/32 ,  C12Q1/527 ,  C12Q1/66 ,  G01N21/78

CPC classification number: C12Q1/527 ,  G01N2333/795 ,  G01N2500/00

Abstract: The invention relates to methods for detecting a soluble guanylate cyclase whose heme iron is in the trivalent oxidation state, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase when the heme iron of at least part of this soluble guanylate cyclase is oxidized to the trivalent state and also to diagnostic aids or kits for detecting a soluble guanylate cyclase with trivalent heme iron. Further, the invention relates methods for detecting a soluble guanylate cyclase lacking a heme group, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase lacking a heme group.

Abstract translation: 本发明涉及用于检测其血红素铁处于三价氧化状态的可溶性鸟苷酸环化酶的方法，以及当该可溶性鸟苷酸环化酶的至少一部分的血红素铁时，发现刺激可溶性鸟苷酸环化酶活性的化学物质的方法 被氧化成三价状态，也用于用三价血红素铁检测可溶性鸟苷酸环化酶的诊断辅助剂或试剂盒。 此外，本发明涉及用于检测缺少血红素基团的可溶性鸟苷酸环化酶的方法，以及用于发现刺激缺少血红素基团的可溶性鸟苷酸环化酶的活性的化学物质的方法。

公开(公告)号：US20050176799A1

公开(公告)日：2005-08-11

申请号：US11104556

申请日：2005-04-13

Applicant: Ursula Schindler ,  Karl Schonafinger ,  Hartmut Strobel

Inventor： Ursula Schindler ,  Karl Schonafinger ,  Hartmut Strobel

IPC: A61K31/415 ,  A61K31/00 ,  A61K31/34 ,  A61P1/00 ,  A61P1/16 ,  A61P3/00 ,  A61P3/10 ,  A61P9/00 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/06 ,  A61P13/00 ,  A61P13/12 ,  A61P25/28 ,  A61P43/00 ,  C07D231/56 ,  C07D307/34 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D417/14 ,  A61K31/416 ,  C07D43/04 ,  C07D45/04 ,  C07D49/04

CPC classification number: C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14

Abstract: The present invention relates to pyrazole derivatives of the formula I, their preparation and their use in pharmaceuticals: in which X, R1, R1a, R2, R3, R4 and n are as defined in the claims, which are useful pharmaceutically active compounds for the therapy and prophylaxis of illnesses, for example of cardiovascular diseases such as hypertension, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I are capable of modulating the body's production of cyclic guanosine monophosphate “cGMP” and are generally suitable for the therapy and prophylaxis of illnesses which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the formula I, to their use for the therapy and prophylaxis of the abovementioned illnesses and for preparing pharmaceuticals for this purpose, and also to pharmaceutical preparations which comprise the compounds of the formula I.

Abstract translation: 本发明涉及式I的吡唑衍生物及其制备及其在药物中的用途：其中X，R 1，R 1a，R 2， R 3，R 4，R 4和n如权利要求中所定义，它们是用于治疗和预防疾病的有用的药物活性化合物，例如心血管 疾病如高血压，心绞痛，心功能不全，血栓形成或动脉粥样硬化。 式I的化合物能够调节身体产生的环鸟苷酸“cGMP”，通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及用于制备式I化合物的方法，其用于治疗和预防上述疾病和用于制备用于该目的的药物，还涉及包含式I化合物的药物制剂。

公开(公告)号：US06759412B2

公开(公告)日：2004-07-06

申请号：US10073203

申请日：2002-02-13

Applicant: Hartmut Strobel ,  Paulus Wohlfart

Inventor： Hartmut Strobel ,  Paulus Wohlfart

IPC: C07C23365

CPC classification number: C07C235/54 ,  C07C233/65 ,  C07C233/74 ,  C07C2602/12

Abstract: The present invention relates to compounds according to the general formula (I), wherein R1-R4 have the meanings given in the description, A is CH2, CHOH or CH—(C1-C3-alkyl), B, C and D are independently CH2 or CH—(C1-C3-alkyl), and R5 is an aryl or heteroaryl group, possibly substituted by the substituents listed in the description. These compounds are useful for the manufacture of medicaments for the treatment of cardiovascular diseases, stable or unstable angina pectoris, coronary heart disease, Prinzmetal angina, acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes, diabetes complications, nephropathy, retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, or restricted memory performance or for a restricted ability to learn, or the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives.

Abstract translation: 本发明涉及根据通式（I）的化合物，其中R 1 -R 4具有说明书中给出的含义，A是CH 2，CHOH或CH-（C 1 -C 3 - 烷基），B ，C和D独立地是CH 2或CH-（C 1 -C 3 - 烷基），R 5是可以被描述中所列取代基取代的芳基或杂芳基。 这些化合物可用于制备用于治疗心血管疾病，稳定或不稳定心绞痛，冠心病，Prinzmetal心绞痛，急性冠状动脉综合征，心力衰竭，心肌梗死，中风，血栓形成，外周动脉闭塞性疾病，内皮功能障碍的药物 ，动脉粥样硬化，再狭窄，PTCA后的内皮损伤，高血压，原发性高血压，肺动脉高压，继发性高血压，肾血管性高血压，慢性肾小球肾炎，勃起功能障碍，室性心律失常，糖尿病，糖尿病并发症，肾病，视网膜病变，血管生成，哮喘支气管炎，慢性肾功能衰竭 ，肝硬化，骨质疏松症或记忆障碍受限或受限制的学习能力，或降低绝经后妇女的心血管危险或摄入避孕药后。

公开(公告)号：US06500631B1

公开(公告)日：2002-12-31

申请号：US09661915

申请日：2000-09-14

Applicant: Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

Inventor： Ursula Schindler ,  Hartmut Strobel ,  Peter Schindler ,  Alexander Muelsch

IPC: C12Q148

CPC classification number: C12Q1/527 ,  G01N2333/795 ,  G01N2500/00

Abstract: The invention relates to methods for detecting a soluble guanylate cyclase whose heme iron is in the trivalent oxidation state, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase when the heme iron of at least part of this soluble guanylate cyclase is oxidized to the trivalent state and also to diagnostic aids or kits for detecting a soluble guanylate cyclase with trivalent heme iron. Further, the invention relates methods for detecting a soluble guanylate cyclase lacking a heme group, and to methods for finding chemical substances which stimulate the activity of a soluble guanylate cyclase lacking a heme group.

Abstract translation: 本发明涉及用于检测其血红素铁处于三价氧化状态的可溶性鸟苷酸环化酶的方法，以及当该可溶性鸟苷酸环化酶的至少一部分的血红素铁时，发现刺激可溶性鸟苷酸环化酶活性的化学物质的方法 被氧化成三价状态，也用于用三价血红素铁检测可溶性鸟苷酸环化酶的诊断辅助剂或试剂盒。 此外，本发明涉及用于检测缺少血红素基团的可溶性鸟苷酸环化酶的方法，以及用于发现刺激缺少血红素基团的可溶性鸟苷酸环化酶的活性的化学物质的方法。

公开(公告)号：US06344468B1

公开(公告)日：2002-02-05

申请号：US09622691

申请日：2000-10-06

Applicant: Ursula Schindler ,  Karl Schoenafinger ,  Hartmut Strobel ,  Viola Groehn

Inventor： Ursula Schindler ,  Karl Schoenafinger ,  Hartmut Strobel ,  Viola Groehn

IPC: A61K314035

CPC classification number: C07D209/48 ,  C07D401/04 ,  C07D409/04

Abstract: The present invention relates to substituted isoindolone derivatives of the formula I, in which R1, R2, R3, R4, R5, R6 and R7 are as defined in the claims, which are useful pharmaceutically active compounds for the therapy and prophylaxis of illnesses, for example cardiovascular diseases such as hypertension, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I are capable of modulating the body's production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of illnesses which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the formula I, to their use for the therapy and prophylaxis of the abovementioned illnesses and for preparing pharmaceuticals for these, and also pharmaceutical preparations which comprise compounds of the formula I.

Abstract translation: 本发明涉及式I的取代的异吲哚酮衍生物，其中R 1，R 2，R 3，R 4，R 5，R 6和R 7如权利要求中所定义，其是用于治疗和预防疾病的有用的药物活性化合物， 例如心血管疾病如高血压，心绞痛，心功能不全，血栓形成或动脉粥样硬化。 式I的化合物能够调节人体产生的环鸟苷酸（cGMP），并且通常适用于治疗和预防与受干扰的cGMP平衡有关的疾病。 本发明还涉及制备式I化合物的方法，其用于治疗和预防上述疾病和用于制备这些疾病的药物，以及包含式I化合物的药物制剂。